|Publication number||US7186567 B1|
|Application number||US 11/266,189|
|Publication date||Mar 6, 2007|
|Filing date||Nov 4, 2005|
|Priority date||Aug 29, 2002|
|Also published as||US7619739|
|Publication number||11266189, 266189, US 7186567 B1, US 7186567B1, US-B1-7186567, US7186567 B1, US7186567B1|
|Inventors||Richard L. Sutherland, Donna M. Brandelik, Christina K. Shepherd|
|Original Assignee||Science Applications International Corporation|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (100), Non-Patent Citations (65), Referenced by (18), Classifications (12), Legal Events (7)|
|External Links: USPTO, USPTO Assignment, Espacenet|
“This application is a divisional application of and claims priority to and incorporates by reference in its entirety application Ser. No. 10/614,188 entitled. “DEVICE AND METHOD FOR DETECTION AND IDENTIFICATION OF BIOLOGICAL AGENTS,” filed Jul. 8, 2003, which application claims priority to and incorporates by reference in its entirety U.S. Provisional patent Application No. 60/406,665 entitled “METHOD AND APPARAUS FOR DETECTION AND ANALYSIS” filed Aug. 29, 2002.”
1. Field of the Invention
The present invention relates generally to a sensor system, and more specifically to a sensor for detecting biological and chemical agents in the environment.
2. Description of the Related Art
Antibody-based detection systems are the most mature and advanced technology for biological agent detection and identification. Antibodies are defined as any of the body immunoglobulins that are produced in response to specific antigens and that counteract their effects by neutralizing toxins, agglutinating bacteria or cells, and precipitating soluble antigens. Antigens are defined as protein or carbohydrate substances capable of stimulating an immune response. Antibodies are very specific and bind only to their target, even in the presence of other material. In a detector, antibodies are normally immobilized on a substrate, e.g., a polymer, such as polyvinylethylene, polyethylene, or polystyrene, for subsequent incubation with the target organism or molecule. Typically, the antibodies are not chemically bound to the substrate, but merely attached by hydrogen bonding or electrostatic charge. The antibody and antigen bind upon contact, thereby immobilizing the antigen. Classically, a second antibody to the target agent incubates, as well as binds to the antigen. This second antibody is generally linked to some type of reporter system, usually an enzyme. The varying forms of these reporter systems include, e.g., fluorescent, magnetic, enzymatic, colorimetric, etc. This transducer provides the means of detecting the presence of the antigen of interest. Enzyme linked immunosorbent assay (ELISA) is based on this process.
An analyte in the antibody-antigen detection system is typically in an aqueous solution or other liquid solution. The aqueous solution must make frequent and intimate contact with the immobilized antibody on the substrate material. A large surface area on the substrate allows a higher density of antibodies and hence a higher sensitivity. However, the antibodies must be tightly bound to the substrate to survive repeated motion of the analyte over the substrate without becoming detached and flushed away with the solution. Therefore, covalent bonding, rather than hydrogen bonding or electrostatic bonding, of the antibodies to the substrate is preferential. Many biological compounds of interest in the system are proteins, e.g., enzymes, hormones, toxins, antibodies, and antigens. Proteins are composed of amino acids, having both an amino group (NH2) and a carboxylic acid group (COOH). A substrate functionalized with one or both of these groups can be activated to chemically bind antibodies.
The introduction of a second antibody in the ELISA process complicates and slows down the detection/identification process. A physical property change produced by the antibody-antigen chemical reaction provides the basis for a more direct transduction mechanism. The transduction mechanism in an optics-based detection system is based on a change in absorption or index of refraction, which is monitored by the optical system.
Several detectors are based on a change of index of refraction. One such sensor is based on surface plasmon resonance. Surface plasmon techniques are difficult to integrate for multiplexed operation where multiple target agents can be monitored simultaneously. Also, their sensitivity cannot be engineered by sharpening the spectral or angular response to light.
Other known sensors include a chemical sensor based on porous silicon and a porous-semiconductor-based, e.g., porous Si, optical interferometric sensor. Interference filters can be made with porous silicon. However, porous silicon interference filters are incompatible with polymer waveguide technology and hence cannot be readily integrated onto a polymer waveguide chip. Also, porous polymers are easier to apodize, i.e., sharpen, their spectral response using holographic techniques. Moreover, polymer chemistry is more adaptable to functionalization with chemical groups for binding antibodies and antigens. Most immunosorbent assays are conducted on polymer substrates. Porous silicon has not been widely used for this application. No conventional methods propose the simultaneous use of porous semiconductors as both chemical and optical filters.
Another known sensor is a doubly-differential interferometer-based sensor with evanescent wave surface detection. This sensor is a surface detector only and cannot take advantage of the extended surface area of a porous polymer. Furthermore, the sensor also requires polarized light and a modulator. Additionally, this sensor is a part of a system that does not provide for continuously monitoring the environment. The interferometer is also not flexible for sharpening the optical response for higher sensitivity.
Another sensor, in the form of polymerized crystalline colloidal arrays, achieves detection of chemical and biological agents by a change in diffraction accompanying the swelling or shrinkage of a hydrogel containing the crystalline colloidal array in response to a chemical reaction with target agent(s). Similarly, a conventional hologram-containing sensor consists of a holographic grating recorded preferably in a gelatin, where reaction of chemical agents with the gelatin produces some change in the physical properties of the hologram matrix, thereby changing the diffraction properties of the hologram. In both the polymerized crystalline arrays and the hologram-containing sensor, a matrix containing a grating serves to uptake an analyte, but does not allow for the analyte to flow through the system. Once the system is swollen, the only mechanism for replacing it with new samples is to remove the grating from the system and dry it out. Since the materials used are not porous, the system cannot take advantage of increased surface area to volume ratio and does not provide a convenient method for chemically filtering the analyte. These methods are also not compatible with waveguides for integration onto a chip.
Another chemical and biochemical sensor includes a planar waveguide with a grating coupler. A recognition layer containing specific chemical or biochemical binding partners, e.g., antibodies or antigens, is located on the waveguide. A chemical reaction on the recognition layer changes the effective refractive index of the guiding layer, thereby changing the coupling efficiency of the grating, i.e., the angle of incidence for maximum input coupling to the waveguide. Using this sensor, a method for optical determination of an analyte records the position of light points with a position sensitive detection method. The grating is a surface grating formed by standard methods, i.e., photolithographic patterning followed by etching. A surface grating sensor cannot take advantage of the extended surface area of a porous polymer, since the grating cannot be extended throughout the volume of the porous polymer and chemical detector or recognition molecules cannot be dispersed throughout the volume to increase its chemical sensitivity. This system does not provide a mechanism for continuously monitoring the environment by flowing the analyte through the grating, since it is only a surface grating. Nor does the system use the grating as an optical filter to take advantage of the sharp spectral properties of a Bragg grating for detecting large changes in transmission of such a filter with relatively small changes in refractive index.
Summary of the Problem:
The rapid detection and identification of hazardous biological and chemical agents has become an increasing concern due to the dangers of biological and chemical warfare as well as the threat of terrorists releasing such agents in public venues. Before troops are deployed in forward staging areas, biosensors need to assess the environment for force protection. In terrorist situations, adequate security measures require continuous monitoring of high value public areas, such as government buildings, subways, stadiums, water treatment plants, etc. First responders to a biological or chemical terrorist attack need to quickly and accurately detect and identify the particular biological or chemical agent to take necessary precautions and adequately administer aid. Although standoff sensors, such as lidar, provide some remote sensing of the release of agents, they cannot identify particular agents. Point detection systems can sense the immediate environment. Specificity is a necessary ingredient in the sensor system. Compact, rugged, reliable sensor systems that can continuously monitor the environment are desired. With appropriate telemetry systems, these can be deployed in forward battle areas during warfare (for example, delivered by drones or dropped by parachute) or placed in high value public areas to continuously monitor and report environmental changes that may indicate a terrorist attack.
Conventional means of detecting biological agents in the environment, e.g., laser induced fluorescence, accurately detect the presence of biological agents. These detectors do not, however, provide the specificity to identify the agents present. Additionally, these devices are complex and bulky. Other devices capable of agent detection and identification, e.g., mass spectrometry, are expensive and not easily portable. These devices take a considerable amount of time to identify the agent(s). Still other devices, utilizing immunoassay techniques, identify agents with high specificity by antigen-antibody chemical reactions. Unfortunately, these techniques are not readily amenable to providing continuous, always-on monitoring of the environment. Moreover, these techniques are not reagentless; they normally require additional chemistry to add chromophores or fluorescing agents for detection and identification by color change or fluorescence. A need exists for a compact, inexpensive, portable biosensor system that can continuously monitor the environment, i.e., always-on mode, and both detect and identify biological agents in the environment with high specificity and a low false alarm rate.
Summary of the Solution:
The conventional methods neither achieve nor teach methods or devices to meet the above-mentioned criteria for a biosensor. Therefore, it is an object of this invention to provide a compact, inexpensive, rugged and portable biosensor that can continuously monitor the environment for detection and identification of hazardous biological agents.
The solution to the conventional methods is to continuously monitor the environment for hazardous biological and biochemical agents, providing rapid, automatic, simultaneous detection and identification of such agents with high specificity and low false alarm rate. Such a system continuously draw samples from the environment, i.e., air, water, or soil, for analysis. The system repeatedly and indefinitely exposes the detector to the samples. The detector specifically recognizes the target agents and responds by some physical or chemical change of state. Based on the change in the detector state, a transduction mechanism produces a useable signal. The detection mechanism is highly sensitive, achieving a rapid response with low probability of false signals, whether positive or negative indications. The detector is rugged and can reliably respond even after being subjected to multiple sample exposures. The system provides a platform insusceptible to external temperature swings and vibrations.
It is furthermore an object of this invention to monitor air and/or water and/or soil continuously for the detection and/or identification of hazardous biological agents.
It is furthermore an object of this invention to provide a working fluid that is continuously circulated in the sensor as a medium for transporting environmental samples to detector modules for always-on monitoring of the presence of hazardous biological agents.
It is furthermore an object of this invention to provide a detector consisting of a porous polymer Bragg grating that functions simultaneously as a chemical filter, to trap specific target agents for detection by a highly specific chemical reaction with a conjugate molecule, and as an optical filter that provides the transduction mechanism to create a measurable signal stemming from the chemical reaction.
It is furthermore an object of this invention to provide a detector consisting of a porous polymer Bragg grating that has a high surface area to volume ratio to provide a high density of binder molecules that increases the probability of target agent binding and hence increases the detection sensitivity.
It is furthermore an object of this invention to provide a detector consisting of a porous polymer Bragg grating that can be fabricated holographically as a thick filter with low index modulation, hence achieving a sharp spectral transmission or reflection notch that enhances the detection sensitivity.
It is furthermore an object of this invention to provide a detector consisting of a porous polymer Bragg grating that can be fabricated holographically to apodize the filter, sharpen the spectral response and enhance the detection sensitivity.
It is furthermore an object of this invention to provide an array of detector modules consisting of porous polymer Bragg gratings, each of which is sensitized with a different molecule for binding specific target agents and can hence monitor the presence of multiple hazardous biological agents in the environment.
It is furthermore an object of this invention to provide an array of detector modules consisting of porous polymer Bragg gratings, where each module consists of more than one detector arm having said porous polymer Bragg gratings, and only one arm is sensitized with a particular detector molecule, the other arm(s) serving as control and reference that factor out the effects of thermal and light source fluctuations and drift, or other environmental disturbances, and factor out transient effects from inert microscopic material contained in the environmental sample, thereby achieving a low false alarm rate.
It is furthermore an object of this invention to provide a system that does not require additional chemistry to add chromophores or fluorescing agents for detection and identification by color change or fluorescence.
It is furthermore an object of this invention to provide detection sensitivity by combined optical and electronic differential gain.
It is furthermore an object of this invention to provide a sensor capable of rapid response due to high detection sensitivity.
A first embodiment of the present invention describes a method of determining a target agent in an environment comprising the steps of obtaining a first sample from the environment and introducing the first sample to at least one detection module. The first sample is then filtered through at least a first filter and a second filter comprising at least one detection module, wherein the first filter contains at least one detection molecule for the target agent and the second filter contains no detection molecules for the target agent. An optical property is measured from the first filter and the second filter after filtering the first sample there through. Comparing the measured optical property of the first filter to the measured optical property of the second filter assists in determining the presence of the target agent.
A second embodiment of the present invention describes a sensor for determining the presence of at least one target agent in a sample comprising a collector system for collecting the sample from an environment, a transfer system for adding the sample to a working fluid, a dispenser system for introducing the working fluid, including the sample, to a detector system, and a detector system comprising at least one detector module. The detector module includes at least a first optical grating and a second optical grating, wherein the first optical grating contains at least one detector molecule for detecting the at least one target agent and the second optical grating does not contain a detector molecule for detecting the at least one target agent. The detector module further includes at least a first measuring device for measuring an optical response of the first optical grating after contact with the working fluid, including the sample, and at least a second measuring device for measuring an optical response of the second optical grating after contact with the working fluid, including the sample. A processor compares the measured optical response from the at least a first measuring device to the measured optical response from the at least a second measuring device to determine the presence of the target agent.
A third embodiment of the present invention describes a detector module for detecting a target agent within a sample comprising at least one inlet reservoir for receiving the sample therein, a first micro-fluidic channel integrally connected to the at least one inlet reservoir, a second micro-fluidic channel integrally connected to the at least one inlet reservoir, a first optical grating physically integrated with the first micro-fluidic channel and a second optical grating physically integrated with the second micro-fluidic channel, wherein the first optical grating includes at least one detector molecule for detecting the target agent within the sample and the second optical grating does not include a detector molecule for detecting the target agent within the sample. The detector module also comprises at least one outlet reservoir physically integrated with the first micro-fluidic channel for removing the sample from the detector module.
A fourth embodiment of the present invention describes a method for forming an optical sensor for sensing the presence of a target agent in a sample comprising interfering a first coherent beam and a second coherent beam within a polymerizable polymer-dispersed liquid crystal material forming a polymerized hologram containing liquid crystals within a polymer matrix. The liquid crystals are extracted from the polymer matrix forming pores therein. The binding sites within the pores are chemically activated for receipt of a detector molecule therein. A detector molecule is attached within the pores for sensing the presence of a target agent in a sample.
The present invention will be more clearly understood from a reading of the following description in conjunction with the accompanying figures wherein:
In an embodiment of the present invention as shown in
The dual-function ID subsystem 70 sends the sample data from the DMA through an electronic signal 80 to a data storage subsystem 90. Data storage subsystem 90 obtains and continuously compiles data from the DMA. The data within data storage subsystem 90 may either be accessed directly or may be sent via an appropriate transmission system, such as telemetry subsystem 110, for recording and analysis. The transmission system may send data at pre-selected intervals in batch format or, alternatively, may send data on a continual basis. Further still, the data storage system 90 may perform analysis on the data from the ID subsystem 70 prior to forwarding for transmission. With this embodiment, the data storage subsystem 90 may be programmed to transmit data when a particular result is found, e.g., a target agent has been identified.
As a second function, after passing through the ID subsystem 70, the working fluid 50 is transferred to a recirculation subsystem 120. Recirculation subsystem 120 decontaminates the working fluid 50 and returns the working fluid 50 to the transfer subsystem 30 to obtain another environmental sample. The recirculation subsystem 120 consists of an ultrafine filter and an ultraviolet lamp that destroys/removes foreign material remaining in the working fluid. The working fluid is passed through micro-tubing and a low-flow pump. The working fluid then returns to the transfer subsystem 30 to pick up another sample 40 of the environment. The constant sampling and recirculation allows the system to continuously monitor the environment. In essence, it is “always on.”
At the onset of the system of sensor 10, collection subsystem 20 has an air sampler, preferably consisting of a pump for drawing through air from the environment, a horn or similar instrument for directing the air flow, a filter stage consisting of one or more filters to remove large particles, e.g., greater than 10 μm, and an exhaust system. For sampling gases and aerosols in the air, the collection subsystem 20 is adapted from conventional air samplers such as those provided by Airmetrics, Mattson-Garvin, SKC, or Sceptor Industries. For sampling water, e.g., standing water, wastewater, etc., the collection subsystem 20 is adapted from conventional water samplers such as the Markland Duckbill® Sampling System, or an equivalent supplied by such companies as Global Water Instrumentation, Inc., and others. In one embodiment, the water sampler consists of a remote sampler head submerged in the water or a tube submerged in the water. A sampler pump/controller draws water samples through a filter stage to remove large particles, e.g., greater than 10 μm. The water sample is then retained in a holding container for transfer of microscopic agents to the working fluid. The water is then flushed out of the system to make room for the next sample. For sampling soil, the collection subsystem 20 is adapted from conventional soil water samplers such as those supplied by Soil Monitoring Engineering. Soil water samplers, such as lysimeters or porous ceramic cups, are buried in the soil. A pump creates a partial vacuum, which causes water in the surrounding soil to enter the sampler via a porous ceramic filter. The sample is then retained in a holding container for transfer of microscopic agents to the working fluid. The water is then flushed out of the system to make room for the next sample.
The environmental samples are transferred to a working fluid by a transfer subsystem 30. The transfer subsystem 30 transfers potentially hazardous microscopic agents, as well as other microscopic constituents, from the environment to working fluid 50 of the sensor 10. Transfer subsystem 30 may be adapted from conventional products. For gas/water transfers, the transfer subsystem 30 is adapted from conventional gas bubblers, such as those supplied by SKC. The air sample is bubbled through the working fluid, and gases from the atmosphere are dissolved in the fluid. For aerosol/water transfers, the transfer subsystem 30 is adapted from conventional particle impingers, such as those supplied by SKC. Aerosol particles impinge on the working fluid and become trapped in the liquid. For water/water transfers, the transfer subsystem 30 is adapted from conventional dialysis cells, such as the DMLS™ supplied by Margan. The gradient of concentrations allows for material dissolved in the environmental water to diffuse into the working fluid 50 contained in the dialysis cell.
The working fluid 50 is typically an aqueous solution compatible with the molecular detectors. The working fluid 50 continuously flows through the system to provide an always-on monitoring device. Although the working fluid 50 necessarily comes into contact with the environment, it must be held at a constant temperature and appropriate chemical composition, e.g., pH, to optimize the sensor 10 and enhance the lifetime of the complex detector molecules, e.g., antibody proteins. A heater or a thermoelectric cooler system controls the temperature of the working fluid for optimum operation of about 30–40° C.
Dispenser subsystem 60 receives the working fluid from transfer subsystem 30. Referring to
The detector module 305 identifies agents in the working fluid 50. Micro-pipette dispensers 310 at a sample arm inlet reservoir 311 and control arm inlet reservoir 312 on the module 305 introduce the working fluid 50 containing potentially hazardous agents, as well as other inert material, to the module 305. Each reservoir 311, 312 typically holds 100–1000 nL of solution. Micro-fluidic channels 315 having exemplary cross sectional areas of approximately 10×10 μm2 to 100×100 μm2, direct the solution, i.e., working fluid and inert materials, in the sample and control arms to porous polymer Bragg gratings 320, 321. Pressure gradients, or alternatively, electrokinetics, may induce fluid flow within the micro-fluidic channels 315. In the case of electrokinetic inducement, additional electrodes in the module move the solution along the channel by electrophoresis and/or electroosmosis. The porous Bragg gratings 320, 321 allow the solution to flow through. An outlet micro-pipette 325 collects the material at the outlet reservoir 326. Proper filtering in the collection subsystem 20 and dispenser subsystem 60 of
In addition to the Bragg gratings 320, 321, 322 described above, each module 305 consists of an optical channel waveguide 335 comprised of three arms: (1) a sample arm 330, (2) a control arm 331, and (3) a reference arm 332. All three arms contain identically fabricated porous polymer Bragg gratings 320, 321, 322. The porous polymer Bragg gratings 320, 321, 322 have been integrated onto the module along with a light source 340, waveguides 335, waveguide splitters 345, 346, micro-fluidic channels 315, photodetectors (i.e., photodiodes) 350, 351, 352 and processing electronics 360. The response from each arm 330, 331, 332 is continuously and simultaneously monitored and processed electronically to factor out environmental disturbances, including inert material in the sample, to achieve a high sensitivity and a low false alarm rate.
Light is launched into the waveguide from the light source 340, which may be a broadband light emitting diode (“LED”) or preferably a single-frequency laser diode (“LD”). At the first Y-splitter 345, a portion of the light is directed to the reference arm 332 containing a reference grating, and subsequently, a photodetector 352. The reference grating is hermetically sealed; it never is exposed to the working fluid 50. The reference grating may or may not contain a pure solution in its pores. The optical properties (e.g., index of refraction) of the reference grating change only due to thermal changes in the system. The light detected by the photodetector 352 in this arm 332 changes only due to thermally induced changes in the reference grating, energy fluctuations, or drift of the light source. The remaining energy at the first Y-splitter 345 is directed to a second Y-splitter 346 where the energy is split into two equal parts and directed to the sample 330 and control 331 arms of the detector module 305.
The sample 330 and control 331 arms contain the activated sample grating 320 and the unactivated control grating 321, respectively. The location of the porous polymer Bragg gratings 320, 321, 322 may be in the channel waveguide or in the waveguide cladding that form the sample 330, control 331, and reference 332 arms. Each grating is constructed to reflect light at the same wavelength over a very narrow spectral band. Foreign material passing through the filters produces modifications to the refractive index. The modifications shift the spectral location of the reflection notch and produce a change in the transmitted light detected by the photodetectors 350, 351. Energy detected at the photodetectors 350, 351 will also change due to thermal drift of the reflection notch or light source fluctuations. The fluctuations are removed by taking the difference of the sample grating 320 and control grating 321 signals. Alternatively, the processing electronics 360 can subtract the reference grating arm 332 signal from both the sample grating 330 and control grating 331 arm signals. Since all three gratings 320, 321, 322 and their respective photodetectors 350, 351, 352 are located on the same module 305, the gratings 320, 321, 322 experience the same fluctuations due to thermal drift, light source fluctuations, and other disturbances. This process thus removes spurious signals due to the detector environment. The reference grating arm 332 can also maintain the wavelength of the light source tuned to the Bragg grating 322. As the Bragg grating notch drifts due to thermal drift, the signal from the reference grating arm 332 passes through a feedback loop to the light source 340 to tune the wavelength of the source to the notch wavelength of the Bragg grating 322. The remaining signals are the result of foreign material, i.e., agents, present in the working fluid. Inert material passes through the gratings and produces transient changes in the refractive index. As a result, transient signal responses are produced at the photodetectors 350, 351. The signals from the sample grating 330 and control grating 331 arms are integrated over an appropriate time interval (e.g., by sample and hold circuits) and then subtracted (e.g., by a differential amplifier). Since both arms, 330 and 331, identify, on the average, the same amount of inert material, these signals will cancel, producing a null signal. However, if target agents, i.e., molecules, are present, the target agents stick to the sample grating 320 and permanently change its refractive index. Moreover, the refractive index change increases with each captured target agent. Since the reflection notch is spectrally narrow, a relatively small change in refractive index produces a large change in filter transmittance. The subsequent change in the transmitted light over the integration interval upsets the balance in the two arms 330 and 331. The difference signal is passed through a differential amplifier in the electronic processor 360. The presence of a non-zero signal heralds the presence of the target agent. Once a target agent detection is accomplished, that specific detector module 305 is replaced before the system is used in another monitoring scenario.
In addition to the component parts of the detection module 305 shown in
The Bragg gratings 420, 421, 422 are situated in the channel waveguide 435. To form the Bragg gratings 420, 421, and 422, a rectangular cavity is etched in the channel waveguide 435 at the position selected for each of the gratings. This cavity is then filled with a pre-polymer syrup described herein, and a porous polymer grating is formed by the procedures discussed further with respect to at least
Referring to an alternative embodiment in
Alternatively, the Bragg gratings 520, 521, 522 are situated in the cladding directly above the channel waveguide 535. The SiO2 layer 580 containing the SiON channel waveguide 535 is coated with a polymer cladding 590. A rectangular cavity is etched in the polymer cladding 590 at the positions selected for the gratings. This cavity is then filled with a pre-polymer syrup described herein, and a porous polymer grating is formed by the procedures discussed further with respect to at least
With respect to
Further, waveguides 435, 445, 446, 447, 535, 545, 546, and 547 may be formed of SiON as a core material. Depending on the nitrogen-to-oxygen ratio, the refractive index of SiON can be varied between 1.46 and 2.3. Thus, the SiON refractive index can be tuned to be greater than that of SiO2 to form a waveguide. And, the refractive index can be matched to that of the polymer (approximately 1.52) used in the inline Bragg gratings, or tuned to be slightly larger than the polymer that is used as the cladding layer. Thus, it is possible to tune the index so that the porous polymer Bragg gratings can be situated directly in the channel waveguide, or in the waveguide cladding directly above the channel waveguide as described herein.
In further reference to
The sample and hold circuits 600, 601 sample voltages from the photodetectors over a specified time interval. The time interval is selected by a negative pulse of a predetermined time interval applied to the gate of a p-channel MOSFET 670, which closes a switch and allows data in the form of a stream of voltage pulses from photodiodes to pass through the switch and be stored on a capacitor 620, 625. These pulses, as illustrated in the embodiment in
The above scheme also discriminates real signals from photodiode voltage fluctuations and drift that may occur due to light source power fluctuations, thermal drift, and other environmental disturbances. Since the two detector arms reside on the same module, they are subject to the same external disturbances. Voltages produced due to these effects are common to both channels and subtracted out by the differential amplifier.
Voltage drift due to external influences may also be factored out by using the output of the reference arm of the module in a set of circuits similar to those of
To discriminate fluctuations and drift of the Bragg grating from those of the light source, in an alternative embodiment, the reference arm could be replaced with a dual reference arm using an additional Y-splitter. For example, referring to
In an alternative embodiment of the present invention, referring to
Changes in the refractive index of the grating affect the efficiency of the coupling at a specific wavelength. Referring to
In an alternative embodiment, a single Bragg grating in a waveguide channel can be used as a stand-alone detector element. Referring to top and side views,
As referenced previously herein, certain embodiments of the present invention utilize polymer-dispersed liquid crystal (“PDLC”) or holographic PDLC (“HPDLC”) related technology in the formation of the Bragg gratings and waveguide components. Descriptions of PDLC materials and related technology can be found in U.S. Pat. No. 5,942,157, U.S. patent application Ser. No. 09/363,169 filed on Jul. 29, 1999 for Electrically Switchable Polymer Dispersed Liquid Crystal Materials Including Switchable Optical Couplers and Reconfigurable Optical Interconnects, U.S. patent application Ser. No. 10/235,622 filed on Sep. 6, 2002 for Electrically Switchable Polymer Dispersed Liquid Crystal Materials Including Switchable Optical Couplers and Reconfigurable Optical Interconnects, U.S. application Ser. No. 10/303,927 filed on Nov. 26, 2002 for Tailoring Material Composition for Optimization of Application-Specific Switchable Holograms, and U.S. patent application Ser. No. 60/432,643 filed on Dec. 12, 2002 for Switchable Holographic Polymer Dispersed Liquid Crystal Reflection Gratings Based on Thiol-ene Photopolymerization, each of which is incorporated by reference herein in its entirety. In a preferred embodiment of the present invention, the Bragg gratings comprise static holograms formed through holographic polymerization of a PDLC material using coherent light beams. As is described above with reference to
In a further embodiment of the present invention, described herein is the structure and formation of the Bragg gratings. Referring to
The selected Bragg wavelength is determined by such factors as the chosen laser wavelength and the spectral region of sensitivity desired for detecting a refractive index shift based on the polymer and detector molecule reaction selected. This optical region may be anywhere across the visible or near infrared spectrum. The grating period Λ is selected by forming a hologram with a recording wavelength λr and an angle of incidence θr of the incident beams, with Λ=λr/2sinθr. Thus, either λr or θr, or both, can be varied to form the desired grating period. The Bragg wavelength λB for light propagating substantially along the waveguide axis is approximately 2nΛ, where n is the average refractive index of the medium at λB. The index n changes as target agents are bound to the polymer matrix. The Bragg wavelength λB is given by:
The bandwidth δλ of the spectral diffraction efficiency for a Bragg grating is given by:
where κ is the coupling constant of the grating and L is the grating thickness. The coupling constant is further given by κ=πn1/λB, where n1 is the amplitude of the index modulation of the grating. For sufficiently thin gratings, the bandwidth is inversely proportional to the thickness. Thus, a thicker grating leads to a sharper reflection notch. The thicker grating also increases the diffraction efficiency. For sufficiently thick gratings, the bandwidth is directly proportional to κ. Thus, a small coupling constant κ (i.e., a small index modulation) also leads to a narrow spectral notch. Generally, a thick filter with a small index modulation yields a grating with high peak diffraction efficiency and a narrow spectral notch.
The index modulation of the grating is produced by the periodic variation of nanoscopic pores throughout the volume of the polymer. Typically, the density of pores has the form of a rectangular wave, with a volume fraction of pores ƒc in a channel of width αΛ, (0<α<1) and no pores in adjacent channels of width (1−α)Λ. The index modulation is related to the first Fourier component of the Fourier expansion of this rectangular wave, and is given by:
where np and ns are the refractive indices of the polymer and solution filling the pores, respectively. The parameters ƒc and α are determined by the phase separation of liquid crystal during the recording of the holographic grating. These are controlled by processing parameters such as recording intensity and total exposure, as well as material properties including liquid crystal concentration and concentrations of other recipe constituents, such as long chain aliphatic acids. With the refractive indices relatively fixed at np approximately equal to 1.52 and ns approximately equal to 1.33, the index modulation is directly controlled by the values of ƒc and α.
The presence of sidelobes 1600, such as those shown in
As exemplified in
Sensitivity is built into the detection in two ways. First, there is an optical differential gain. The filter reflection or transmission notch is very sharp spectrally and exhibits a large change in transmittance for a relatively small change in refractive index. Second, there is an electronic differential gain. Signals from the sample and control arms are detected and processed in an electronic differential amplifier that produces a large output for a relatively small difference between the two signals. See
To build specificity into the sample gratings, the binding sites of the pores or polymer matrix of the holograms are chemically activated and the detector molecules are bound to the polymer matrix. Thus, if a target agent is present in the working solution, it will selectively bind to the detector molecules. The target agent becomes trapped in the pore. Since the chemical nature of the polymer matrix changes, the average refractive index also changes. Consequently, the spectral properties of the porous polymer Bragg grating also change.
Bound target agents modify the spectral properties of the sample grating by changing the refractive index and possibly swelling the polymer. The diffraction efficiency of the sample grating is very sensitive to these changes. The spectral shift ΔλB of the grating is determined by
For example, let the Bragg wavelength be λB=850 nm for a grating with an average index n=1.5 and grating period Λ=283 nm. Thus, a spectral shift of ΔλB=1 nm is produced by Δn/n=ΔΛ/Λ=0.0012,i.e., Δn=0.00183, or ΔΛ=0.33 nm. A spectral shift of 1 nm produces a very significant change in the transmittance of the filter. Referring to
The sensitivity of the sample grating may be enhanced by interrogating the grating at a wavelength near a region of rapidly changing efficiency. The diffraction efficiency η(i.e., reflection; transmission equals 1−η) for a Bragg grating is given by:
where κ is the coupling coefficient and L is the filter thickness. The relative change Δη/η in diffraction efficiency is given by:
for changes in refractive index and grating period, respectively. Referring to
The following embodiments are set forth herein to describe exemplary materials and grating configurations that were useful as detectors in experiments conducted in free space. One skilled in the art recognizes the configuration changes necessary to incorporate such examples into the waveguide embodiments contemplated by the present invention.
In a first exemplary embodiment, gratings are constructed using thiol-acrylate as the polymerizable monomer and 2-carboxyethylacrylate (2-CEA) as the binding site monomer, with 10-μm thickness achieved by sandwiching the mixture between two glass plates. These gratings have one glass substrate coated with a release agent. The release agent substrate is removed, and the gratings are evacuated in a vacuum oven over a period of approximately three days to remove the liquid crystal. The cells are scanned in, for example, a Cary 500 UV/VIS spectrophotometer from Varian. The sensor molecule Gliadin is bound to the grating to sense the anti-Gliadin target agent. Before attachment of Gliadin to the carboxy (COOH) group of the HPDLC, the carboxy group is activated using the EDC/NHS coupling procedure. After activation of the groups, the Gliadin is attached. Following attachment, another protein, casein, is used to block carboxy groups that were not attached to Gliadin. Casein does not interfere with the target agent attachment, since the anti-Gliadin antibodies are specific for Gliadin.
In a second exemplary embodiment, a batch of HPDLC gratings are made on BK7 optical flats at 25-μm thickness. The gratings are evacuated over approximately three days to remove the liquid crystal. Certain gratings from the batch are checked with an ELISA (Enzyme Linked Immuno Specific Assay) kit, and other gratings are scanned in a spectrometer for a peak shift. The ELISA checked gratings and the spectrometer scanned gratings are tested with either standard A or standard F. The pre-selected spectral absorbance is proportional to concentration, i.e., A is the lowest concentration and F is the highest. The HPDLC gratings withstand treatment with all the solutions needed for protein and antibody attachment without degrading.
Exemplary embodiments involve a grating sensing anti-Gliadin, or an alternative embodiment sensing Cortisol. Materials used in the exemplary embodiments include the monomer dipentaerythritol hydroxy penta acrylate (DPHPA), photoinitiator dye Rose Bengal (RBAX), co-initiator N-phenylglycine (NVG), monomer N-vinylpyrrollidone (NVP), long-chain aliphatic acid dodecanoic acid (DDA), binding site monomer 2-carboxyethylacrylate (2-CEA), and liquid crystals E7 and TL213 (both available from Merck).
Gliadin, an antigen derived from wheat, is utilized as the sensor molecule to detect the presence of anti-Gliadin. The recipe includes 47.9% DPHPA, 0.6% RBAX, 1.5% NPG, 10.0% NVP, 38.0% E7, and 2.0% 2-CEA. The above formula, less the 2-CEA, is a conventional formulation for recording HPDLC gratings, and is given the designation CS573. A holographic recording in such a mixture results in a periodic distribution of interconnected liquid crystal droplets. The addition of 2-CEA provides COOH groups attached to the polymer matrix, with some COOH groups residing at the polymer/liquid crystal droplet interfaces. The pre-polymer mixture also includes 15 μm glass rods that act as spacers for the holographic cell which comprises two 1″-diameter, ⅛″-thick glass windows. A sonicator homogenizes the mixture prior to sandwiching the pre-polymer mixture within the holographic cell, between the glass windows. At least one of the glass windows is coated with a release agent to facilitate removal of one substrate after holographic recording. Alternatively, reflection holograms are recorded (in cells designated CS573-x, where x=1 . . . 9) using two 532-nm beams derived from the same frequency-doubled Nd: YVO4 laser at an optical power of approximately 15 mW/cm2 for 30 seconds. A 1-hour white-light post-cure procedure bleaches the remaining RBAX dye.
Following post-cure, the release-agent-coated flat is separated from the photopolymerized material, and the transmittance spectrum of each photopolymerized material is measured using, for example, a Cary500 UV/VIS/NIR spectrometer. The nominal peak of the reflection notch (minimum of the transmittance curve) is around 535 nm. The holograms are placed in a vacuum oven (approximately 28 mm Hg) for a period of about 48 hours to extract the liquid crystal. After removing the holograms from the oven, the samples are rinsed in methanol and replaced in the oven for 3 hours. Each cell is then measured again in the Cary500. All samples exhibit a blue shift of the diffraction peak, indicating that the liquid crystal is removed, and the refractive index of the composite medium is decreased.
Following these measurements, six cells (x=2, 3, 5, 6, 8, 9) are selected for further tests and one additional cell (x=1) is reserved for a control experiment. The set of six cells are divided into two subsets of three (subset A: x=3, 5, 6 and subset B: x=2, 8, 9). Table 1 below describes the procedures applied to the cells. The binding of present antibodies, formation of the sandwich complexes, and enzymatic color reaction take place during three different reaction phases.
In Phase I, solution samples containing different concentrations of target molecules are pipetted onto the Bragg gratings. Any present target agents bind to the inner surface of the Bragg grating. After a 30-minute incubation the grating is washed with wash buffer for removing non-reactive components. Phase I includes incubation with Gliadin (I w/G) or no incubation with Gliadin (I w/o G).
Processing of Bragg Gratings for Gliadin–Anti-Gliadin Testsa
a‘x’ denotes that part of the procedure that was used.
bUnits/milliliter (U/mL) of IgA are the concentration units used by the supplier of the test kit.
After the Phase I treatment, sample Bragg gratings in subsets A and B are air-dried overnight. All sample Bragg gratings exhibit a red shift of the diffraction notch, with the non-Gliadin samples having about twice the shift of that of the Gliadin samples, due to the increased refraction index. In all cases, material, e.g., Gliadin and/or casein, is added to the vacant pores of the sample, attaching to the activated COOH sites, and thereby increasing the refractive index. The molecular weight of Gliadin is approximately 50,000 Daltons. Casein, a protein found in milk, exists most often as a micelle, with an average molecular weight of approximately 375,000 Daltons. Thus, sample Bragg gratings containing only casein have more mass and thus a higher refractive index than those sample Bragg gratings containing a mixture of casein and Gliadin. A higher refractive index implies a larger shift of the diffraction notch.
Following anti-Gliadin (IgA) incubation, sample Bragg gratings 3 and 2 are air-dried overnight. Both sample Bragg gratings exhibit an additional shift, indicating the binding of the anti-Gliadin to the Gliadin. All four spectrometer transmission scans in the above sequence for sample Bragg grating 3, as exemplified in
Sample Bragg gratings 5, 6, 8, 9 and control 1 are subjected to Phases II and III of the procedure. In Phase II the sample Bragg gratings are incubated in an anti-human-IgA horseradish peroxidase conjugate solution, which recognizes IgA class antibodies bound to the immobilized antigens. A wash buffer then washes away any excess enzyme conjugate not specifically bound to the antibodies.
In Phase III, a chromogenic substrate solution containing TMB (3,3′,5,5′-Tetramethylbenzidine) is dispensed onto the gratings. During incubation, the color of the solutions changes from a clear solution to blue. The addition of 1 M hydrochloric acid stops color development to stabilize the sample for spectrometer measurements. The solution changes color to yellow. The amount of color is proportional to the concentration of IgA antibodies present in the original sample. A higher concentration of IgA produces a larger absorbance at 450 nm. The color changes of sample Bragg gratings 5, 6, 8, 9 and control 1 are quantified by measuring the absorbance of the samples at 450 nm. In all cases, sample Bragg gratings 5 and 8, both treated with Gliadin, exhibit larger absorbance than cells not treated with Gliadin (6 and 9), with the larger difference being between sample Bragg gratings 8 and 9 that are exposed to the higher concentration of IgA. The control sample Bragg grating 1 exhibits an absorbance similar to sample Bragg grating 6, which follows since neither sample Bragg grating was treated with Gliadin. Finally, a solution of TMB and HCI is formed without any exposure to the sample Bragg gratings. This solution exhibits no absorbance at 450 nm.
In another exemplary embodiment, cortisol is the antigen and the sample Bragg grating is activated with anti-cortisol to form a detector sensitive to the presence of cortisol. Cortisol is a hormone present in the body and released in higher quantities during stressed or agitated states. Designated CS576, the recipe included 51.9% DPBPA, 0.6% RBAX, 1.5% NPG, 10.0% NVP, 4.0% DDA, 30.0% TL213, and 2.0% 2-CEA. The mixture also includes 8-μm glass rods as spacers for the holographic cell, and a sonicator homogenizes the mixture. The resulting syrup is then sandwiched between two 1″-diameter, ⅛″-thick glass windows. At least one of the glass windows is coated with a release agent to facilitate removing one of the substrates. Reflection holograms are prepared using 532-nm beams. A 1-hour white-light post-cure bleaches remaining RBAX dye. One substrate is removed from each of the sample Bragg gratings and the gratings are scanned in the Cary500. The nominal notch wavelength is 536 nm. After liquid crystal removal, the sample Bragg gratings are then split into four groups for further treatment: (A) anti-cortisol attachment with subsequent incubation in cortisol; (B) anti-cortisol attachment with no subsequent incubation in cortisol; (C) no antibody attachment with subsequent incubation in cortisol; and (D) anti-cortisol attachment with subsequent incubation in Gliadin. Two sample Bragg gratings from each group (A)–(D) are subjected to the entire cortisol test, consisting of attachment, incubation, spectrometer measurements of diffraction notch, and color test. The remaining two sample Bragg gratings from groups (A)–(D) are run only through the diffraction notch test.
Sample Bragg gratings in groups (A), (B), and (D) are subjected to the same attachment procedure, while no antibody (anti-cortisol) is added to the sample Bragg gratings in group (C). At the conclusion of these procedures, all of the sample Bragg gratings are measured using the Cary500. In all samples, the diffraction notch red shifts approximately 6% due to the increased refractive index as mass, i.e., anti-cortisol and/or casein, was added to the vacant pores.
Sample Bragg gratings in groups (A), (C), and (D) are then incubated in cortisol, and all sample Bragg gratings are re-measured with the Cary500. Only sample Bragg gratings in group (A) (the only group treated with anti-cortisol attachment and cortisol incubation) exhibit a red shift (approximately 1%), indicating the binding of cortisol to anti-cortisol thereby increases the mass in the pores and thus increasing the refractive index.
Two sample Bragg gratings from groups (A), (B), and (C) are subjected to a color test verfication. The color test consists of a competitive reaction between the antigen, i.e., cortisol, and an enzyme-conjugated antigen, i.e., anti-cortisol. Sample Bragg gratings in groups (A) and (C) are incubated in equal volumes of the antigen and the enzyme-conjugated antigen, while group (B) sample Bragg gratings are incubated in the enzyme-conjugated antigen only. Antigen and enzyme-conjugated antigen molecules bind with present antibodies in proportion to their relative concentration. When the chromogenic solution containing TMB is added, TMB reacts with the enzyme-conjugated antigen, inducing a color change. HCI is again added to stop the reaction and stabilize the sample Bragg gratings for subsequent spectrometer runs. Hence, sample Bragg gratings with a higher proportion of enzyme-conjugated antigens exhibit a stronger color change, i.e., have a higher absorbance at 450 nm. Thus, the absorbance at 450 nm is inversely proportional to the concentration of antigen, i.e., cortisol, present, as exemplified in the test results in
The embodiments described herein are intended to be exemplary, and while including and describing the best mode of practicing, are not intended to limit the invention. Those skilled in the art appreciate the multiple variations to the embodiments described herein which fall within the scope of the invention.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US3580655||Oct 23, 1965||May 25, 1971||Battelle Development Corp||Wavefront reconstruction|
|US3658526||Aug 25, 1969||Apr 25, 1972||Du Pont||Hologram recording in photopolymerizable layers|
|US3667946||Sep 23, 1970||Jun 6, 1972||Holotron Corp||Surface treatment of photopolymer film used for recording holograms|
|US3758186||Nov 30, 1966||Sep 11, 1973||Battelle Development Corp||Method of copying holograms|
|US4003629||Jul 16, 1975||Jan 18, 1977||Siemens Aktiengesellschaft||Coupling device for light waves|
|US4006963||Jul 21, 1975||Feb 8, 1977||Siemens Aktiengesellschaft||Controllable, electro-optical grating coupler|
|US4018228||Feb 24, 1975||Apr 19, 1977||Goosen Carl C||Surgical punch apparatus|
|US4045124||Feb 25, 1975||Aug 30, 1977||Xerox Corporation||Bistable deflection system|
|US4124947||Nov 8, 1976||Nov 14, 1978||Adolf Kuhl||Graphic pattern or the like and method of producing the same|
|US4210132||Jul 26, 1978||Jul 1, 1980||The Kendall Company||Artificial sphincter|
|US4368736||Nov 17, 1980||Jan 18, 1983||Kaster Robert L||Anastomotic fitting|
|US4374371||Jan 17, 1980||Feb 15, 1983||Kearney-National, Inc.||Cadmium electric fuse|
|US4416540||Nov 23, 1981||Nov 22, 1983||Peter Nicholson||Apparatus and method for holographic contact copying|
|US4560249||Apr 18, 1983||Dec 24, 1985||Sumitomo Electric Industries, Ltd.||Method of forming diffraction gratings and optical branching filter elements produced thereby|
|US4688900||Sep 17, 1985||Aug 25, 1987||Kent State University||Light modulating material comprising a liquid crystal dispersion in a plastic matrix|
|US4728547||Nov 21, 1986||Mar 1, 1988||General Motors Corporation||Liquid crystal droplets dispersed in thin films of UV-curable polymers|
|US4809713||Oct 28, 1987||Mar 7, 1989||Joseph Grayzel||Catheter with magnetic fixation|
|US4810063||Mar 19, 1986||Mar 7, 1989||Manchester R & D Partnership||Enhanced scattering voltage sensitive encapsulated liquid crystal with light directing and interference layer features|
|US4818070||Jan 15, 1988||Apr 4, 1989||Asahi Glass Company Ltd.||Liquid crystal optical device using U.V.-cured polymer dispersions and process for its production|
|US4832424||Oct 29, 1985||May 23, 1989||Mcgrew Stephen P||White-light viewable, cylindrical holograms and method of spatially filtering wavefronts|
|US4844613||Nov 2, 1987||Jul 4, 1989||Stc Plc||Optical surface plasmon sensor device|
|US4856876||Jun 23, 1986||Aug 15, 1989||Manchester R & D Partnership||Fluorescent colored encapsulated liquid crystal apparatus using enhanced scattering|
|US4857425||Jun 26, 1987||Aug 15, 1989||Holtronic Technologies Limited||Manufacture of integrated circuits using holographic techniques|
|US4891152||Dec 28, 1987||Jan 2, 1990||Hughes Aircraft Company||Dispersion of liquid crystal droplets in a photopolymerized matrix and devices made therefrom|
|US4923269||Jan 28, 1988||May 8, 1990||British Telecommunications Public Limited Company||Bidirectional optical space switch|
|US4929240||Dec 21, 1987||May 29, 1990||University Of New Mexico||Surgical clip and applier|
|US4930674||Feb 24, 1989||Jun 5, 1990||Abiomed, Inc.||Surgical stapler|
|US4938568||Jan 5, 1988||Jul 3, 1990||Hughes Aircraft Company||Polymer dispersed liquid crystal film devices, and method of forming the same|
|US4942102||Jun 22, 1989||Jul 17, 1990||E. I. Du Pont De Nemours And Company||Holographic optical elements having a reflection hologram formed in a photopolymer|
|US4983176||Mar 6, 1989||Jan 8, 1991||University Of New Mexico||Deformable plastic surgical clip|
|US5003386||Dec 8, 1989||Mar 26, 1991||Ilford Limited||Preparation of a copy hologram with a light modulating array derived from a master hologram|
|US5011624||Dec 19, 1989||Apr 30, 1991||Yamagishi Frederick G||Acrylate polymer-dispersed liquid crystal material and device made therefrom|
|US5014709||Jun 13, 1989||May 14, 1991||Biologic Systems Corp.||Method and apparatus for high resolution holographic imaging of biological tissue|
|US5015249||Dec 26, 1989||May 14, 1991||Nakao Naomi L||Endoscopic stapling device and method|
|US5047040||Feb 16, 1989||Sep 10, 1991||Devices For Vascular Intervention, Inc.||Atherectomy device and method|
|US5084203||Mar 13, 1991||Jan 28, 1992||Hoechst Celanese Corp.||Light transmissive liquid crystalline composite exhibiting a high Kerr effect|
|US5096282||Mar 23, 1990||Mar 17, 1992||Hughes Aircraft Co.||Polymer dispersed liquid crystal film devices|
|US5105298||Jul 12, 1989||Apr 14, 1992||Board Of Trustees, Leland Stanford Jr. University||Birefringent structures formed by photo-exposure of polymer films and method for fabrication thereof|
|US5136666||Aug 6, 1991||Aug 4, 1992||The University Of Colorado Foundation, Inc.||Fiber optic communication method and apparatus providing mode multiplexing and holographic demultiplexing|
|US5144690||Dec 3, 1990||Sep 1, 1992||Corning Incorporated||Optical fiber sensor with localized sensing regions|
|US5166813||Jul 11, 1990||Nov 24, 1992||Nygene Corporation||Optical evaluation using a hologram barrier filter|
|US5170925||Mar 18, 1991||Dec 15, 1992||Ethicon, Inc.||Laparoscopic stapler with knife means|
|US5174276||Nov 20, 1989||Dec 29, 1992||Hillway Surgical Limited||Endoscope device for applying an aneurysm clip|
|US5182180||Aug 27, 1991||Jan 26, 1993||E. I. Du Pont De Nemours And Company||Dry film process for altering the wavelength of response of holograms|
|US5182665||Sep 7, 1990||Jan 26, 1993||Displaytech, Inc.||Diffractive light modulator|
|US5188638||Feb 6, 1992||Feb 23, 1993||Tzakis Andreas G||Apparatus and method for preforming anastomosis fastener securement of hollow organs|
|US5198912||Jul 10, 1991||Mar 30, 1993||Polaroid Corporation||Volume phase hologram with liquid crystal in microvoids between fringes|
|US5210630||Aug 13, 1992||May 11, 1993||U.S. Philips Corporation||Liquid-crystal display device|
|US5227859||Dec 4, 1990||Jul 13, 1993||Grumman Aerospace Corporation||Passive coherent radiation detection system|
|US5227906||Mar 8, 1990||Jul 13, 1993||Canon Kabushiki Kaisha||Optical switch array capable of bidirectional signal transfer between a plurality of terminals|
|US5234447||Aug 28, 1990||Aug 10, 1993||Robert L. Kaster||Side-to-end vascular anastomotic staple apparatus|
|US5235445||Apr 17, 1992||Aug 10, 1993||Ag-Technology Co., Ltd.||Liquid crystal optical element with liquid crystal in polymer matrix with particular modulus of elasticity|
|US5240636||Mar 30, 1992||Aug 31, 1993||Kent State University||Light modulating materials comprising a liquid crystal microdroplets dispersed in a birefringent polymeric matri method of making light modulating materials|
|US5258008||Jul 29, 1992||Nov 2, 1993||Wilk Peter J||Surgical stapling device and associated method|
|US5264950||Jan 6, 1992||Nov 23, 1993||Kent State University||Light modulating device with polarizer and liquid crystal interspersed as spherical or randomly distorted droplets in isotropic polymer|
|US5270843||Aug 31, 1992||Dec 14, 1993||Jiansheng Wang||Directly formed polymer dispersed liquid crystal light shutter displays|
|US5272550||Sep 2, 1992||Dec 21, 1993||International Business Machines Corporation||Hologram system|
|US5291317||Jul 12, 1990||Mar 1, 1994||Applied Holographics Corporation||Holographic diffraction grating patterns and methods for creating the same|
|US5299289||Jun 11, 1992||Mar 29, 1994||Matsushita Electric Industrial Co., Ltd.||Polymer dispersed liquid crystal panel with diffraction grating|
|US5303322||Mar 11, 1993||Apr 12, 1994||Nioptics Corporation||Tapered multilayer luminaire devices|
|US5313317||Oct 9, 1992||May 17, 1994||Nippondenso Co., Ltd.||Hologram|
|US5323251||Oct 28, 1992||Jun 21, 1994||Merck Patent Gesellschaft Mit Beschrankter Haftung||Electrooptical liquid crystal system|
|US5328800||May 6, 1992||Jul 12, 1994||Fuji Photo Film Co., Ltd.||Color image forming method using silver halide, reducing agent, polymerizable compound and colorant|
|US5330264||May 1, 1992||Jul 19, 1994||Nippondenso Co., Ltd.||Method and apparatus for copying and manufacturing hologram plate|
|US5330486||Nov 25, 1992||Jul 19, 1994||Wilk Peter J||Laparoscopic or endoscopic anastomosis technique and associated instruments|
|US5354498||Dec 9, 1992||Oct 11, 1994||Fuji Xerox Co., Ltd.||Phase separation liquid crystal polymer|
|US5356557||Mar 13, 1992||Oct 18, 1994||Merck Patent Gesellschaft Mit Beschrankter Haftung||Electrooptical system|
|US5363228||Mar 5, 1993||Nov 8, 1994||General Electric Company||Optical device with spatial light modulators for switching arbitrarily polarized light|
|US5366462||Aug 6, 1993||Nov 22, 1994||Robert L. Kaster||Method of side-to-end vascular anastomotic stapling|
|US5376095||Nov 4, 1993||Dec 27, 1994||Ethicon Endo-Surgery||Endoscopic multi-fire flat stapler with low profile|
|US5377008||Apr 2, 1992||Dec 27, 1994||Battelle Memorial Institute||Integrated optical compensating refractometer apparatus|
|US5384067||May 18, 1992||Jan 24, 1995||Kent State University||Grey scale liquid crystal material|
|US5453338||Mar 30, 1993||Sep 26, 1995||Dai Nippon Printing Co., Ltd.||Hologram and method of and apparatus for producing the same|
|US5471326||Apr 30, 1993||Nov 28, 1995||Northrop Grumman Corporation||Holographic laser scanner and rangefinder|
|US5488681||Sep 9, 1994||Jan 30, 1996||Deacon Research||Method for controllable optical power splitting|
|US5499118||Aug 31, 1994||Mar 12, 1996||Hughes Aircraft Company||System for copying multiple holograms|
|US5529861||Mar 24, 1994||Jun 25, 1996||Tamarack Storage Devices||Method for enhancing the utility of a photopolymer recording media for holographic data recording|
|US5544268||Sep 9, 1994||Aug 6, 1996||Deacon Research||Display panel with electrically-controlled waveguide-routing|
|US5547786||Aug 22, 1994||Aug 20, 1996||Northrop Grumman Corporation||System and method of fabricating multiple holographic elements|
|US5593615||Jun 7, 1995||Jan 14, 1997||Minnesota Mining And Manufacturing Company||Light modulating device having a matrix prepared from acid reactants|
|US5641426||Apr 29, 1994||Jun 24, 1997||Minnesota Mining And Manufacturing Company||Light modulating device having a vinyl ether-based matrix|
|US5648857||Feb 16, 1995||Jul 15, 1997||Nippondenso Co., Ltd.||Manufacturing method for hologram which can prevent the formation of ghant holograms due to noise light|
|US5661533||May 19, 1995||Aug 26, 1997||Advanced Display Systems, Inc.||Ultra fast response, multistable reflective cholesteric liquid crystal displays|
|US5661577||May 15, 1995||Aug 26, 1997||University Of Southern California||Incoherent/coherent double angularly multiplexed volume holographic optical elements|
|US5680233||Nov 28, 1995||Oct 21, 1997||Reveo, Inc.||Image display systems having direct and projection viewing modes|
|US5682214||Dec 13, 1995||Oct 28, 1997||Seiko Epson Corporation||Optical apparatus for controlling the wavefront of a coherent light|
|US5695682||Feb 24, 1997||Dec 9, 1997||Kent State University||Liquid crystalline light modulating device and material|
|US5698134||Jul 27, 1994||Dec 16, 1997||Merck Kgaa||Electrooptical system|
|US5698343||Jun 28, 1996||Dec 16, 1997||The United States Of America As Represented By The Secretary Of The Air Force||Laser wavelength detection and energy dosimetry badge|
|US5706375||Sep 10, 1996||Jan 6, 1998||Jds Fitel Inc.||Variable-attenuation tunable optical router|
|US5725970||Sep 16, 1996||Mar 10, 1998||E. I. Du Pont De Nemours And Company||Broad band reflection holograms and a dry process for making same|
|US5731853||Feb 16, 1996||Mar 24, 1998||Matsushita Electric Industrial Co., Ltd.||Display device|
|US5734485||Apr 25, 1995||Mar 31, 1998||Rocky Research||Large display composite holograms and methods|
|US5748272||Jun 10, 1996||May 5, 1998||Nippon Telegraph And Telephone Corporation||Method for making an optical device using a laser beam interference pattern|
|US5751452||Feb 18, 1994||May 12, 1998||Nippon Telegraph And Telephone Corporation||Optical devices with high polymer material and method of forming the same|
|US5771320||Oct 21, 1996||Jun 23, 1998||Wavefront Research, Inc.||Optical switching and routing system|
|US5832148||Dec 19, 1996||Nov 3, 1998||California Institute Of Technology||Electrically controlled wavelength multiplexing waveguide filter|
|US5852504||Jun 21, 1996||Dec 22, 1998||Fujitsu Limited||Stereoscopic display method of hologram and its forming method and its stereoscopic display apparatus|
|US5862214||Nov 9, 1995||Jan 19, 1999||Lucent Technologies Inc.||Low cost adjustable base stand|
|US6689316 *||May 21, 1999||Feb 10, 2004||Cambridge University Technical Services, Ltd.||Holographic sensors and their production|
|1||A. M. Lackner, et al., "Droplet Size Control in Polymer Dispersed Liquid Crystal Films," SPIE Proceedings, vol. 1080, pp. 53-61, Jan. 17-18, 1989.|
|2||Allan R. Tokuda, et al., "Holocamera for 3-D Micrography of the Alert Human Eye," Applied Optics, vol. 19, No. 13, pp. 2219-2225, Jul. 1, 1980.|
|3||Born and Wolf, "Principles of Optics," 5<SUP>th </SUP>Edition, New York (1975).|
|4||C. C. Bowley, et al., "45.3: Electro-Optic Investigations of H-PDLCS: The Effect of Monomer Functionality on Display Performance," SID International Symposium, Digest of Technical Papers, First Edition, pp. 958-961, May 1999.|
|5||C. C. Bowley, et al., "Advances in Holographic Polymer Dispersed Liquid Crystal Technology," in Liquid Crystal Materials and Devices, Mat. Res. Soc. Symposium Proceedings, vol. 559, pp. 97-107, 1999.|
|6||C. C. Bowley, et al., "Morphology of Holographically-Formed Polymer Dispersed Liquid Crystals (H-PDLC)," Mol. Cryst. Liq. Cryst., vol. 331, pp. 209-216, 1999.|
|7||D. J. Lougnot, et al., "Photopolymers for Holographic Recording: IV. New Self-Processing Formulations Based on beta-Hydroxy Ethyloxazolidone Acrylate," Pure Appl. Opt., vol. 2, pp. 383-392, 1993.|
|8||D. Schwarze-Haller and F. Noack, "Nuclear Magnetic Resonance Field-Cycling Proton Relaxation Study of Polymer Dispersed Liquid Crystals," J. Chem. Phys., vol. 105, No. 11, pp. 4823-4832, Sep. 1996.|
|9||Edited by H. Bennett, "Cooncise Chemical and Technical Dictionary, FAIC" Chemical Publishing Co., Inc., 1974.|
|10||European Search Report for Application No. EP 97 93 7988, dated Oct. 13, 1999.|
|11||G. P. Crawford, et al., "Reflective Color LCDs Based on H-PDLC and PSCT Technologies," Journal of the Society for Information Display, vol. 5, No. 1, pp. 45-48, 1997.|
|12||G. P. Crawford, et al., "Reflective Color LCDs Based on H-PDLC and PSCT Technologies," SID International Symposium, Digest of Applications Papers, pp. 99, May 14-16, 1996.|
|13||G. S. Iannacchione, et al., "Deuterium NMR and Morphology Study of Polymer-Dispersed Liquid-Crystal Bragg Gratings," Europhysics Letters, vol. 36, No. 6, pp. 425-430, 1996.|
|14||G. von Bally, et al., "Gradient-Index Optical Systems in Holographic Endoscopy," Applied Optics, vol. 23, No. 11, pp. 1725-1729, Jun. 1, 1984.|
|15||G. W. Stroke and A. E. Labeyrie, "White-Light Reconstruction of Holographic Images Using the Lippmann-Bragg Diffraction Effect," Physics Letters, vol. 20, No. 4, pp. 368-370, Mar. 1, 1966.|
|16||H. I. Bjelkhagen, et al., "High-Resolution Contact Denisyuk Holography," Applied Optics, vol. 31, No. 8, pp. 1041-1047, Mar. 10, 1992.|
|17||Hideya Murai, et al., "Electro-Optic Properties for Liquid Crystal Phase Gratings," SPIE Proceedings, vol. 1665, pp. 230-239, Feb. 11-13, 1992.|
|18||Hori, Asai, and Fukai, "Field-Controllable Liquid-Crystal Phase Grating," IEEE, vol. ED-16, p. 1734 (4 pp.), 1979.|
|19||International Preliminary Examination Report for Application No. PCT/US00/34661, dated Feb. 20, 2002.|
|20||International Search Report for Application No. PCT/US00/34661, dated Jul. 17, 2001.|
|21||International Search Report for Application No. PCT/US01/40691, dated Sep. 5, 2001 (mailing date).|
|22||International Search Report for Application No. PCT/US97/12577, dated Jan. 14, 1998 (mailing date).|
|23||J. A. Firehammer, et al., "Lasing Pixels: A New Application for Polymer Dispersed Liquid Crystals (PDLCs)," Mol. Cryst. Liq. Cryst., vol. 331, pp. 165-172, 1999.|
|24||J. Liu, et al., "Cross-Link Optimized Cascaded Volume Hologram Array with Energy-Equalized One-to-Many Surface-Normal Fan-Outs," Optics Letters, vol. 22, pp. 1024-1026 (1997).|
|25||J. Zhang, et al., "Switchable Holograms Recorded in Liquid Crystalline Monomers," SPIE, vol. 2042, pp. 238-247 (Jan. 1994).|
|26||J. Zhang, et al., "Switchable Liquid Crystalline Photopolymer Media for Holography," J. Am. Chem. Soc., vol. 114(4), pp. 1506-1507 (1992).|
|27||K. Tanaka, et al., "Holographically Formed Liquid-Crystal/Polymer Device for Reflective Color Display," Journal of the Society for Information Display, vol. 2, No. 1, pp. 37-38, 1994.|
|28||K. Thilo Weitzel,et al., "Hologram Recording in DuPont Photopolymer Films by Use of Pulse Exposure," Optics Letter, vol. 22, No. 24, Dec. 15, 1997.|
|29||L. Domash, et al., "Programmable Beamlet Generator, Dynamic Lens, and Optical Memory Using Electrically Switched Holographic Devices," SPIE Proceedings, vol. 2026, pp. 642-652, Nov. 1993.|
|30||L. V. Natarajan, et al., "Electrically Switchable Holograms Containing Novel PDLC Structures," SPIE Proceedings, vol. 3143, pp. 182-190, Jul. 28-29, 1997.|
|31||L. V. Natarajan, et al., "Electro-Optical Switching Characteristics of Volume Holograms in Polymer Dispersed Liquid Crystals," Journal of Nonlinear Optical Physics and Materials, vol. 5, No. 1, pp. 89-98, Jan. 1996.|
|32||L. V. Natarajan, et al., "Holographic PDLCs for Optical Beam Modulation, Deflection, and Dynamic Filter Applications," SPIE Proceedings, vol. 3292, pp. 44-51, Jan. 28-29, 1998.|
|33||Lawrence H. Domash, "Applications of Dynamic Holograms for Quasi-Volume Storage," SPIE Proceedings, Very Large Optical Memories-Materials and System Architectures, vol. 1773, 5 pp., 1992.|
|34||Lawrence H. Domash, et al., "Switchable-Focus Lenses in Holographic Polymer Dispersed Liquid Crystal," SPIE, vol. 2689, pp. 188-194, May 1996.|
|35||M. Date, et al., "Full-Color Reflective Display Device Using Holographically Fabricated Polymer-Dispersed Liquid Crystal (HPDLC)," Journal of the Society for Information Display (SID), vol. 7, pp. 17-22, 1999.|
|36||M. Escuti, et al., "5.3: A Model of the Fast-Switching Polymer-Stabilized IPS Configuration," SID International Symposium, Digest of Technical Papers, First Edition, pp. 32-35, May 1999.|
|37||N. Kawatsuki and H. Ono, "Electro-Optical Properties of Polymer/(Liquid Crystal) Composite Film Fabricated by Two-Step Phase Separation Method," Chemistry Letters, No. 5, pp. 333-334, 1995.|
|38||N. M. Lawandy, et al., "L1.3: Lasing Pixel PDLC Light Valves for Projection Applications," SID International Symposium, Digest of Technical Papers, First Edition, pp. 1001-1004, May 1997.|
|39||Preliminary Examination Report for Application No. PCT/US01/40691, dated Sep. 10, 2002 (mailing date).|
|40||Preliminary Examination Report for Application No. PCT/US97/12577, dated Sep. 3, 1998 (mailing date).|
|41||R. A. Kashnow and J. E. Bigelow, "Diffraction From a Liquid Crystal Phase Grating," Applied Optics, vol. 12, No. 10, pp. 2302-2304, Oct. 1973.|
|42||R. L. Sutherland, "Optical Limiters, Switches, and Filters Based on Polymer Dispersed Liquid Crystals," SPIE Proceedings, vol. 1080, pp. 83-90, Jan. 17-18, 1989.|
|43||R. L. Sutherland, et al., "Bragg Gratings in an Acrylate Polymer Consisting of Periodic Polymer-Dispersed Liquid Crystal Planes," Chem. Mater., vol. 5, No. 10, pp. 1533-1538, 1993.|
|44||R. L. Sutherland, et al., "Electrically Switchable Volume Gratings in Polymer-Dispersed Liquid Crystals," Appl. Phys. Lett., vol. 64, No. 9, pp. 1074-1076, Feb. 28, 1994.|
|45||R. L. Sutherland, et al., "Switchable Bragg Gratings Formed in situ Within a Polymer-Dispersed Liquid Crystal Composite Medium," Materials Research Society Symp. Proc., vol. 425, pp. 331-341, Apr. 8-11, 1996.|
|46||R. T. Pogue, et al., "Monomer Functionality Effects in the Anisotropic Phase Separation of Liquid Crystals," Polymer 41, pp. 733-741, 2000.|
|47||Richard L. Sutherland, et al., "Analysis of Periodic Polymer-Dispersed Liquid Crystal Structures for Dynamic Hologram Applications," SPIE Proceedings, vol. 2532, pp. 309-318, Jul. 10-12, 1995.|
|48||Richard L. Sutherland, et al., "Development of Photopolymer-Liquid Crystal Composite Materials for Dynamic Hologram Applications," SPIE Proceedings, vol. 2152, pp. 303-313, Jan. 26-28, 1994.|
|49||Richard L. Sutherland, et al., "Switchable Holograms for Displays and Other Applications," SPIE Proceedings, vol. 3421, pp. 8-18, Jun. 1998.|
|50||Richard L. Sutherland, et al., "Switchable Holograms in New Photopolymer-Liquid Crystal Composite Materials," SPIE Proceedings, vol. 2404, pp. 132-143, Feb. 9-10, 1995.|
|51||Richard L. Sutherland, et al., "The Physics of Photopolymer-Liquid Crystal Composite Holographic Gratings," SPIE Proceedings, vol. 2689, pp. 158-169, May 1996.|
|52||Richard T. Ingwall and Timothy Adams, Hologram: Liquid Crystal Composites, SPIE Proceedings, vol. 1555, pp. 279-290, Jul. 24-25, 1991.|
|53||Seferis, James C., "Refractive Indices of Polymers," Polymer Handbook, 4<SUP>th </SUP>Edition, John Wiley & Sons, Inc., pp. 571-582, Copyright 1999.|
|54||Stephen A. Benton, et al., "One-Step White-Light Transmission Holography," SPIE, vol. 212, pp. 2-7, 1979.|
|55||Stephen A. Benton, et al., "One-Step White-Light Transmission Holography," SPIE, vol. 215, pp. 156-161, 1980.|
|56||Stoke, Funkhouser, Leonard, Indebetoew, and Zech, "Hand-Held Holography," 1 p., Sep. 19, 1966.|
|57||T. J. Bunning, et al., "Liquid Crystals for Advanced Technologies," Materials Research Society, pp. 331-343, Apr. 8-11, 1996.|
|58||T. J. Bunning, et al., "Morphology of Reflection Holograms Formed in situ Using Polymer-Dispersed Liquid Crystals," Polymer, vol. 37, No. 14, pp. 3147-3150, 1996.|
|59||T. J. Bunning, et al., "The Morphology and Performance of Holographic Transmission Gratings Recorded in Polymer Dispersed Liquid Crystals," Polymer, vol. 36, No. 14, pp. 2699-2708, 1995.|
|60||Timothy J. Bunning, et al., "The Effects of Eliminating the Chain Extender and Varying the Grating Periodicity on the Morphology of Holographically Written Bragg Gratings," SPIE Proceedings, vol. 2651, pp. 44-54, Jan. 31-Feb. 1, 1996.|
|61||V. N. Mikhailov, et al., "Pulse Hologram Recording in DuPont's Photopolymer Films," SPIE, vol. 3011, pp. 200-202, 1997.|
|62||V. P. Tondiglia, et al., "Volume Holographic Image Storage and Electro-Optical Readout in a Polymer-Dispersed Liquid Crystal Film," Optics Letters, vol. 20, No. 11, pp. 1325-1327, Jun. 1, 1995.|
|63||Written Opinion for Application No. PCT/US01/40691, dated May 15, 2002 (mailing date).|
|64||Written Opinion for Application No. PCT/US97/12577, dated Apr. 28, 1998 (mailing date).|
|65||Yariv, Amnon, "Quantum Electronics, Third Edition," John Wiley & Sons, Copyright 1989, pp. 608-614.|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US7349590 *||Sep 26, 2005||Mar 25, 2008||Corning Incorporated||Polarization modulation interrogation of grating-coupled waveguide sensors|
|US7418162 *||Mar 1, 2007||Aug 26, 2008||Lxsix Photonics Inc.||Method and apparatus for inducing an index of refraction change on a substrate sensitive to electromagnetic radiation|
|US7574082 *||Mar 28, 2007||Aug 11, 2009||Verizon Services Organization Inc.||Optical power monitoring with robotically moved macro-bending|
|US7616851 *||Nov 10, 2009||Lockheed Martin Corporation||Tunable wavelength filter device|
|US7768650 *||Apr 20, 2005||Aug 3, 2010||Michael Bazylenko||Optoelectronic biochip|
|US8014640||Sep 6, 2011||Verizon Patent And Licensing Inc.||Optical power monitoring with robotically moved macro-bending|
|US8053245 *||Nov 19, 2009||Nov 8, 2011||Nanotel Biotechnologies, Inc.||System and method for detecting biochemicals using hydrated substrates based on liquid crystal polymers|
|US8241819 *||Dec 19, 2008||Aug 14, 2012||Smart Holograms Limited||Method for forming a volume holographic sensor in a porous medium|
|US20060197960 *||Apr 20, 2005||Sep 7, 2006||Michael Bazylenko||Optoelectronic biochip|
|US20070147737 *||Mar 1, 2007||Jun 28, 2007||Lxsix Photonics Inc.||Method and apparatus for inducing an index of refraction change on a substrate sensitive to electromagnetic radiation|
|US20070237447 *||Sep 26, 2005||Oct 11, 2007||Mozdy Eric J||Polarization modulation interrogation of grating-coupled waveguide sensors|
|US20080239295 *||Mar 28, 2007||Oct 2, 2008||Verizon Services Organization Inc.||Optical power monitoring with robotically moved macro-bending|
|US20090098467 *||Dec 19, 2008||Apr 16, 2009||Christopher Robin Lowe||Holographic Sensor Based on a Volume Hologram in a Porous Medium|
|US20090244524 *||Jun 10, 2009||Oct 1, 2009||Verizon Services Organization Inc.||Optical power monitoring with robotically moved macro-bending|
|US20100167283 *||Sep 6, 2007||Jul 1, 2010||Adrian Martin Horgan||Analyte Detection|
|US20110130969 *||Nov 23, 2010||Jun 2, 2011||Jacques Gollier||Resonant-Wavelength Measurement Method For Label-Independent Scanning Optical Reader|
|WO2010030251A2 *||Sep 15, 2009||Mar 18, 2010||Agency For Science, Technology And Research||Integrated optical sensors operating in the frequency domain|
|WO2010030251A3 *||Sep 15, 2009||Jun 24, 2010||Agency For Science, Technology And Research||Integrated optical sensors operating in the frequency domain|
|U.S. Classification||436/532, 436/531, 252/582, 435/287.7, 252/299.01|
|Cooperative Classification||G03H2250/38, G03H2001/0264, G01N33/54366, G01N21/774|
|European Classification||G01N33/543K, G01N21/77B3|
|Nov 4, 2005||AS||Assignment|
Owner name: SCIENCE APPLICATIONS INTERNATIONAL CORPORATION, CA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SUTHERLAND, RICHARD;BRANDELIK, DONNA;SHEPHERD, CHRISTINAK.;REEL/FRAME:017189/0015;SIGNING DATES FROM 20030703 TO 20030708
|May 29, 2007||CC||Certificate of correction|
|Oct 11, 2010||REMI||Maintenance fee reminder mailed|
|Oct 20, 2010||FPAY||Fee payment|
Year of fee payment: 4
|Oct 20, 2010||SULP||Surcharge for late payment|
|Apr 11, 2014||AS||Assignment|
Owner name: LEIDOS, INC., VIRGINIA
Effective date: 20130927
Free format text: CHANGE OF NAME;ASSIGNOR:SCIENCE APPLICATIONS INTERNATIONAL CORPORATION;REEL/FRAME:032662/0776
|Sep 5, 2014||FPAY||Fee payment|
Year of fee payment: 8